Divergent Transcriptomic Effects of Allopregnanolone in Postpartum Depression.

Brexanolone, a formulation of the neurosteroid allopregnanolone (ALLO), is approved for treating postpartum depression (PPD) and is being investigated for therapeutic efficacy across numerous neuropsychiatric disorders. Given ALLO's beneficial effects on mood in women with PPD compared to healthy control women, we sought to characterize and compare the cellular response to ALLO in women with ( = 9) or without ( = 10, i.e.

Intrinsically dysregulated cellular stress signaling genes and gene networks in postpartum depression.

Postpartum depression (PPD) is a leading cause of morbidity and mortality among women. Clinically, the administration and withdrawal of supraphysiologic estradiol and progesterone (E2 + P) can cause affective symptom reoccurrence in women with a history of PPD, but not matched controls. To investigate the cellular basis underlying this differential affective response, lymphoblastoid cell lines (LCLs) were derived from women with and without past PPD and compared transcriptomically in hormone conditions mimicking pregnancy and parturition: supraphysiologic E2 + P-addback; supraphysiologic E2 + P-withdrawal; and no added E2 + P (Baseline).

Altered estradiol-dependent cellular Ca homeostasis and endoplasmic reticulum stress response in Premenstrual Dysphoric Disorder.

Premenstrual Dysphoric Disorder (PMDD) is characterized by debilitating mood symptoms in the luteal phase of the menstrual cycle. Prior studies of affected women have implicated a differential response to ovarian steroids. However, the molecular basis of these patients' differential response to hormone remains poorly understood.

In vitro model of perimenopausal depression implicates steroid metabolic and proinflammatory genes.

The estimated 20-30% of women who develop perimenopausal depression (PMD) are at an increased risk of cardiovascular and all-cause mortality. The therapeutic benefits of estradiol (E2) and symptom-provoking effects of E2-withdrawal (E2-WD) suggest that a greater sensitivity to changes in E2 at the cellular level contribute to PMD. We developed an in vitro model of PMD with lymphoblastoid cell lines (LCLs) derived from participants of a prior E2-WD clinical study.

Prdm3 and Prdm16 cooperatively maintain hematopoiesis and clonogenic potential.

Mds1-Evi1 (also known as Prdm3) and Prdm16 are two highly related zinc finger transcription factors that, within the hematopoietic system, are both expressed primarily in hematopoietic stem cells (HSCs). Our laboratory previously found that constitutive Mds1-Evi1 knockout mice are viable, but their HSCs are unable to withstand myeloablative chemotherapy or effectively transplant irradiated recipient mice. A similar phenotype has been observed for Prdm16, except that the Prdm16 constitutive knockout is lethal.

Live-animal imaging of native haematopoietic stem and progenitor cells.

The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions. It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow.

Sex, Drugs, and the Medial Amygdala: A Model of Enhanced Sexual Motivation in the Female Rat.

Methamphetamine (METH) is a psychomotor stimulant that is reported to enhance sexual desire and behavior in both men and women, leading to increases in unplanned pregnancies, sexually-transmitted infections, and even comorbid psychiatric conditions. Here, we discuss our rodent model of increased sexually-motivated behaviors in which the co-administration of METH and the ovarian hormones, estradiol and progesterone, intensify the incentive properties of a sexual stimulus and increases measures of sexually-motivated behavior in the presence of an androgen-specific cue. We then present the neurobiological mechanisms by which this heightened motivational salience is mediated by the actions of METH and ovarian hormones, particularly progestins, in the posterodorsal medial nucleus of the amygdala (MePD), a key integration site for sexually-relevant sensory information with generalized arousal.

Methamphetamine alters DNMT and HDAC activity in the posterior dorsal medial amygdala in an ovarian steroid-dependent manner.

Methamphetamine (Meth) is a psychomotor stimulant associated with increased sexual drive and risky sexual behaviors in both men and women. Females are comparatively understudied, despite the fact that are just as likely as men to use methamphetamine. Importantly, Meth-associated sexual behaviors put female-users at a greater risk for unplanned pregnancies, and increase the risk of psychiatric co-morbidities such as depression.

Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility.

Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice.

Androgen-primed castrate males are sufficient for methamphetamine-facilitated increases in proceptive behavior in female rats.

Methamphetamine (MA) is a psychomotor stimulant associated with increases in sex drive in both men and women. Women, however, are far more likely to face social disadvantages as a consequence of MA use, and their increased sexual motivation poses additional health concerns such as unplanned pregnancies. To better understand the mechanisms underlying MA-facilitated sexual motivation in females, we previously established a rodent model where a "binge"-type administration paradigm of MA to sexually receptive female rats significantly increases proceptive behavior in the presence of a sexually active, gonadally-intact male.